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The viscoelasticity of the cytoplasm plays a critical role in cell morphology, cell division, and intracellular transport. Viscoelasticity is also interconnected with other biophysical properties, such as temperature, which is known to influence cellular bioenergetics. Probing the connections between intracellular temperature and cytoplasmic viscoelasticity provides an exciting opportunity for the study of biological phenomena, such as metabolism and disease progression. The small length scales and transient nature of changes in these parameters combined with their complex interdependencies pose a challenge for biosensing tools, which are often limited to a single readout modality. Here, we present a dual-mode quantum sensor capable of performing simultaneous nanoscale thermometry and rheometry in dynamic cellular environments. We use nitrogen-vacancy centers in diamond nanocrystals as biocompatible sensors for in vitro measurements. We combine subdiffraction resolution single-particle tracking in a fluidic environment with optically detected magnetic resonance spectroscopy to perform simultaneous sensing of viscoelasticity and temperature. We use our sensor to demonstrate probing of the temperature-dependent viscoelasticity in complex media at the nanoscale. We then investigate the interplay between intracellular forces and the cytoplasmic rheology in live cells. Finally, we identify different rheological regimes and reveal evidence of active trafficking and details of the nanoscale viscoelasticity of the cytoplasm.

Sensors that harness quantum mechanical effects can enable high sensitivity and high spatial resolution probing of their environment. The nitrogen-vacancy defect in diamond, a single, optically accessible electronic spin, is a promising quantum sensor that can operate in soft and living systems and provides nanoscale spatial resolution when hosted inside a diamond nanoparticle. Nanodiamond quantum sensors are nontoxic, amenable to surface functionalization, and can be introduced into a variety of living systems. The optical readout of the spin provides detailed information about the local electromagnetic and thermal environment in a noninvasive way. In this Perspective, we introduce the different modalities that nanodiamond quantum sensors offer, highlight recent progress in quantum sensing of biological systems, and discuss remaining challenges and directions for future efforts. [ABSTRACT FROM AUTHOR]